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Biomedical subjects

J Singh

Publications and source records attributed to J Singh.

At least 217 records · Page 12Linked to original sources

Sensitive quantitation of chromium-DNA adducts by inductively coupled plasma mass spectrometry with a direct injection high-efficiency nebulizer.

A novel method is described for the sensitive detection of chromium-DNA adducts. Chromium-DNA adducts were determined in 1 microgram of DNA from normal human lung fibroblasts exposed to sodium chromate using microscale flow injection analysis with a direct injection high-efficiency nebulizer and inductively coupled plasma mass spectrometry detection. The frequency of Cr-DNA adducts increased in a dose-dependent sigmoidal manner, indicating saturation and toxicity. The low detection limits (on the order of parts per trillion) allows the detection of as few as two Cr adducts per 10,000 bases, which, coupled with the small DNA sample requirement, makes this technique suitable for measuring metal-DNA adducts as biomarkers of exposure to toxic and carcinogenic metals such as Cr, in cultured cells, animals, and humans.

Chromium↗

Biliary stenting is more effective than sphincterotomy in the resolution of biliary leaks.

BACKGROUND: Biliary fistulae may occur following surgical injury, abdominal trauma, or inadequate closure of a cystic duct stump. These leaks are most often managed by drainage of the associate biloma and either endoscopic sphincterotomy or placement of a biliary endoprosthesis to decrease the pressure gradient between the bile duct and the duodenum created by the muscular contraction of the ampullary sphincter. In a previous study, we demonstrated a statistically significant reduction in ductal pressures following stent placement as compared to sphincterotomy. The goal of this present study was to determine if reduction in ductal pressures correlates clinically with the resolution of biliary leaks in an animal model. METHODS: Fourteen mongrel dogs underwent laparotomy, cholecystectomy without closure of the cystic stump, and a lateral duodenotomy to identify the major papilla. The dogs were then randomized into three groups. Group I (n = 5) was a control group undergoing closure of the duodenotomy only. Group II (n = 4) underwent sphincterotomy. Group III (n = 5) underwent placement of a 7 Fr x 5 cm biliary endoprosthesis prior to duodenotomy closure. A drain was placed adjacent to the cystic duct stump in all groups. Drain output was recorded daily. The biliary leak was considered resolved when the output was < 10 cc/day. Regardless of suspected fistula closure, the drains were not removed until 2 weeks postprocedure. Necropsy was performed to identify undrained intraperitoneal bile. Statistical analysis was performed using Student's paired t test. RESULTS: All dogs had bile leaks identified on postoperative day 1. The number of days required for resolution of bile leak in group I (mean +/- SEM) was 7.60 +/- 0.87 days, as compared to 6.75 +/- 0.80 days for group II and 2.60 +/- 0.24 days for group III. There was no significant difference in the duration of bile leak between groups I and II (p = 0.445). Group III, however, had a significant reduction in the duration of biliary fistulae as compared to both groups I and II (p < 0.005). At autopsy, persistent bilomas were identified in 80% of group I, 25% of group II, and 0% of group III. None of the dogs showed evidence of dehisence of the duodenotomy closure site as a source of bile leak. CONCLUSION: Biliary stenting significantly reduces the time to resolution of cystic duct leaks as compared to sphincterotomy in a canine model. The results obtained in this study support the use of biliary endoprostheses in the management of biliary leaks and fistulae.

Animals↗

Pretreatment with allopurinol diminishes pancreatography-induced pancreatitis in a canine model.

BACKGROUND: The role of oxygen-derived free radicals in the pathogenesis of pancreatitis has been supported by data from previous studies using animal models. This study was conducted to determine whether prophylaxis with the xanthine oxidase inhibitor allopurinol would decrease the incidence and severity of pancreatography-induced pancreatitis in a canine model. METHODS: Thirty-two dogs were randomized to receive either placebo or oral allopurinol 1 hour before the procedure. A laparotomy and duodenotomy were performed and a pancreatogram was obtained. Postoperatively, pancreatic enzymes were drawn for 5 days. The animals were then euthanized, and the pancreas was weighed and evaluated histologically. RESULTS: The histologic incidence of pancreatitis was significantly reduced in the allopurinol pretreatment group (6.7%) as compared with the placebo group (41.2%, p < 0.01). A significant decrease in postoperative serum amylase levels among dogs pretreated with allopurinol was also noted. A similar trend was observed in lipase levels. The pancreas weight index was decreased in the allopurinol pretreatment group as well (control = 0.00246 vs. allopurinol = 0.00195, p < 0.02). CONCLUSIONS: Pretreatment with oral allopurinol decreases the incidence of pancreatography-induced pancreatitis. These results support the role of xanthine oxidase inhibitors in the prevention of endoscopic retrograde cholangiopancreatography-induced pancreatitis.

Allopurinol↗

Relationship of cesarean delivery to lower birth weight-specific neonatal mortality in singleton breech infants in the United States.

OBJECTIVE: The preferred route of delivery for breech presentation has been controversial. We compared the birth weight-specific neonatal mortality of vaginal births to cesarean births in singleton births with breech presentation. METHODS: A total of 371,692 singleton live births with breech presentation were selected for the study from the United States birth cohorts for the years 1989-1991. Differences in birth weight specific mortality were compared using a z-statistic for differences in proportions and by logistic regression. RESULTS: Compared to primary vaginal births, primary cesarean births had significantly lower neonatal mortality for all birth weight groups, despite increased prevalence of fetal malformations in the cesarean as compared with vaginally delivered group. This mortality difference was greatest in the first hour of life. Difference in overall neonatal (less than 28 days) mortality rate ranged from a low of 1.6-fold in the 500-749 g group (726.6 per 1000 vaginal births compared with 456.3 per 1000 cesarean births, P < .001) to as high as about three-fold in the 1250-1499 g group (232.9 per 1000 vaginal births compared to 72.5 per 1000 cesarean births, P < .001). In the group with birth weights over 2500 g, neonatal mortality in the primary vaginal births was 5.3 per 1000 and in the primary cesarean births, 3.2 per 1000 (P < .001). Similarly, repeat cesarean births had significantly lower birth weight-specific neonatal mortality, compared with vaginal births after previous cesarean. CONCLUSION: Singleton live births with breech presentation delivered by cesarean had lower birth weight-specific neonatal mortality as compared with vaginal births.

Abnormalities, Multiple↗

Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat.

An investigation was made of the effect of Momordica charantia fruit juice on the distribution and number of alpha, beta and delta cells in the pancreas of streptozotocin (STZ)-induced diabetic rats using immunohistochemical methods. The results indicated that there was a significant (Student's t-test, P < 0.004) increase in the number of beta cells in M. charantia-treated animals when compared with untreated diabetics, however, their number was still significantly less than that obtained for normal rats. There was also a significant (P < 0.006) increase in the number of delta cells in STZ-diabetic rats compared to non-diabetic rats. This increase in the number of delta cells was not affected by M. charantia treatment. The number of alpha cells did not change significantly in M. charantia-treated rats when compared with untreated diabetic rats. Our results suggest that oral feeding of M. charantia fruit juice may have a role in the renewal of beta cells in STZ-diabetic rats or alternately may permit the recovery of partially destroyed beta cells.

Animals↗

A radioimmunoassay combined with solid-phase extraction for the determination (pg ml-1) of AR-C15849XX) in human plasma.

A radioimmunoassay has been developed for the determination of AR-C15849KF, a CCK-8 analogue, in human plasma. The method incorporates solid-phase sample extraction, is suitable for the determination of the analyte at pg ml-1 concentrations and is based on a method developed and validated for dog plasma. The solid-phase extraction, using ion-exchange aminopropyl and octadecyl sorbents sequentially, was retained for this procedure to remove matrix interferences in the plasma and to enhance method sensitivity. The calibration range is 10-500 pg ml-1, using a 1 ml sample of undiluted human plasma. The method has been successfully used to generate early human pharmacokinetic data during a programme of exploratory development.

Animals↗

Synergistic effect of iontophoresis and a series of fatty acids on LHRH permeability through porcine skin.

The effect of chemical penetration enhancers (e.g., fatty acids) in combination with iontophoresis was examined on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through porcine skin. Porcine epidermis was pretreated with either ethanol (EtOH) or 10% fatty acid/EtOH. The permeability coefficient of LHRH was significantly (p < 0.05) greater through EtOH, lauric acid/EtOH, palmitic acid/EtOH, oleic acid/EtOH, linoleic acid/EtOH, and linolenic acid/EtOH treated epidermis than the control (untreated epidermis). Iontophoresis further enhanced the permeability of LHRH (p < 0.05) through enhancer-pretreated epidermis in comparison with corresponding passive permeability. Among saturated fatty acids tested, 10% palmitic acid/iontophoresis showed the highest permeability coefficient [(59.52 +/- 2.40) x 10(-4) cm/h], which was approximately 16-fold higher than that of the control [(3.57 +/- 0.41) x 10(-4) cm/h]. Unsaturated cis-octadecenoic acids were more effective penetration enhancers when compared with octadecanoic acid. Among cis-octadecenoic acids in combination with EtOH, the greater iontophoretic permeability coefficient [(59.18 +/- 12.43) x 10(-4) cm/h] was obtained through linolenic acid treated epidermis, which was significantly greater (p < 0.05) than through saturated octadecanoic acid treated epidermis [(29.08 +/- 3.18) x 10(-4) cm/h]. Also, pretreatment of epidermis with 5% linolenic acid/propylene glycol (PG) resulted in greater (p < 0.05) iontophoretic flux of LHRH in comparison to 5% linolenic acid/EtOH. Furthermore, increases in the degree of unsaturation in octadecenoic acids did not produce corresponding increases in the degree of enhancement. Reversibility studies revealed that the postrecovery passive flux of LHRH through 5% linolenic acid in combination with EtOH or PG/iontophoresis treated epidermis was significantly (p < 0.05) reduced than the prerecovery value but could not completely recover to the baseline flux (i.e., flux of LHRH through untreated epidermis).

Animals↗

Haematological and biochemical studies on experimental Theileria annulata infection in crossbred calves.

Administration of ground-up tick tissue stabilate (0.75 tick equivalent) by the subcutaneous route to crossbred calves aged 1 week to 1 month led to the development of acute theileriosis. Haematological studies revealed significant progressive decreases in haemoglobin concentration, packed cell volume and red blood cell count, whereas the total leukocyte count showed an initial non-significant leukocytosis followed by a significant leukopenia. Analysis of serum revealed significant increases in levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine kinase and gamma-glutamyltransferase, and in the concentrations of uric acid, blood urea nitrogen and bilirubin. The concentrations of total protein, albumin, glucose, cholesterol and calcium showed non-significant decreases, while phosphorus decreased significantly during the terminal stages of the disease.

Alanine Transaminase↗

Mechanism of transport enhancement of LHRH through porcine epidermis by terpenes and iontophoresis: permeability and lipid extraction studies.

PURPOSE: The purpose of this study was to investigate the effect of 5% terpenes (i.e., limonene, carvone, thymol, and cineole)/ethanol (EtOH) and iontophoresis on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through the porcine epidermis and biophysical changes in the stratum comeum (SC) lipids by fourier transform infrared (FT-IR) spectroscopy. Methods. The porcine epidermis was pretreated with enhancer for 2 h. The permeability measurement system included Franz diffusion cells, Ag/AgCl electrodes, and SCEPTOR iontophoretic power source. FT-IR spectroscopy was performed to assess the possible contribution of lipid extraction to the transport enhancement of LHRH. RESULTS: Terpenes in combination with EtOH significantly (p < 0.05) increased the flux of LHRH in comparison with the control (epidermis which was not enhancer treated). Iontophoresis further enhanced (p < 0.05) the flux of LHRH through terpenes/EtOH treated epidermis in comparison with their passive permeability. Reversibility studies showed that the post-recovery passive flux of LHRH through 5% limonene in EtOH/iontophoresis treated epidermis was significantly (p < 0.05) decreased but did not significantly recover to the baseline flux (i.e., flux through control epidermis). The SC treated with terpenes/ EtOH showed a decrease in peak heights and areas for both asymmetric and symmetric C-H stretching absorbances in comparison to untreated SC. A greater percent decrease in peak heights and areas was obtained by limonene/EtOH. However, treatment of the SC with terpenes/EtOH followed by iontophoresis did not further decrease the percentage of peak height and area over and above terpene/EtOH suggesting that iontophoresis alone does not cause SC lipid extraction. CONCLUSIONS: Terpenes/EtOH increased LHRH permeability by enhancing the extraction of the SC lipids. Iontophoresis synergistically enhanced the permeability of LHRH through terpenes/EtOH treated epidermis. Thus, terpenes can be used as chemical enhancers in combination with iontophoresis to enhance the transdermal delivery of peptides such as LHRH.

Administration, Cutaneous↗

Anti-myeloma activity of pamidronate in vivo.

Two patients with progressive myeloma were treated with pamidronate disodium every 2-4 weeks. Pamidronate therapy resulted in a significant reduction of marrow plasmacytosis and plasma cell labelling index (PCLI), together with durable (> or = 20 months) stabilization of immunoglobulin (Ig) levels and an increase in bone mineral density in the first patient and > 50%, reduction in Ig levels and bone marrow plasmacytosis in the second. This, to our knowledge, is the first report of an anti-myeloma effect of bisphosphonates in humans and provides evidence that a therapeutic intervention largely directed at the myeloma microenvironment may alter the natural history of the disease.

Aged↗

RNA-mediated regulation of Bc1-2 and cyclin 'D' genes in human platelets.

The aim of this study was to understand the RNA-mediated regulation of genes coding for Bc1-2 and cyclin 'D'. Evidence was provided that these genes are regulated by receptor-C(k)-dependent signalling in human platelets. Further experiments to resolve the mechanism through which receptor-C(k) regulates these genes revealed that receptor-C(k)-dependent signalling is involved in the cleavage of a 125-kDa protein present in endoplasmic reticulum, resulting in generation of a 47-kDa factor that has affinity for a genomic sterol regulatory element as well as the platelet mRNA pool. Based upon these findings we propose a receptor-C(k) dependent signalling pathway for the regulation of Bc1-2 and cyclin 'D' genes at the post-transcriptional level.

Journal Article↗